The variability of the harlequin mouse phenotype resembles that of human mitochondrial-complex I-deficiency syndromes.
The variability of the harlequin mouse phenotype resembles that of human mitochondrial-complex I-deficiency syndromes.
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DOI：
10.1371/journal.pone.0003208
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发表时间：
2008-09-15
期刊：
影响因子：
3.7
通讯作者：
Rustin P
中科院分区：
文献类型：
--
作者：
Bénit P;Goncalves S;Dassa EP;Brière JJ;Rustin P
尽管在了解线粒体疾病的分子基础方面取得了相当大的进展，但迄今为止还没有开发出有效的治疗方法。忠实的动物模型将对设计这种治疗非常有帮助。我们之前表明，Harlequin小鼠表型是由于细胞凋亡诱导因子（Apoptosis Inducing Factor, Aif）蛋白缺失导致的特定线粒体复合物I缺乏。在这里，我们对丑角鼠的表型进行了详细的评估，包括各种组织的生化异常。我们观察到考虑到严重程度和时间进程进展的高度可变的疾病表达。在每个组织中，异常与呼吸链复合体I 20 kDa亚基的残留量相关，而与残留的Aif蛋白无关。除骨骼肌中抗氧化酶活性有中度升高外，其他部位均正常。因此，丑角鼠表型似乎是由线粒体呼吸链复合体I缺乏引起的。其特征与人类复合体I缺乏综合征相似。丑角鼠有望成为开发复合I缺乏综合征治疗方法的模型。
Despite the considerable progress made in understanding the molecular bases of mitochondrial diseases, no effective treatments have been developed to date. Faithful animal models would be extremely helpful for designing such treatments. We showed previously that the Harlequin mouse phenotype was due to a specific mitochondrial complex I deficiency resulting from the loss of the Apoptosis Inducing Factor (Aif) protein. Here, we conducted a detailed evaluation of the Harlequin mouse phenotype, including the biochemical abnormalities in various tissues. We observed highly variable disease expression considering both severity and time course progression. In each tissue, abnormalities correlated with the residual amount of the respiratory chain complex I 20 kDa subunit, rather than with residual Aif protein. Antioxidant enzyme activities were normal except in skeletal muscle, where they were moderately elevated. Thus, the Harlequin mouse phenotype appears to result from mitochondrial respiratory chain complex I deficiency. Its features resemble those of human complex I deficiency syndromes. The Harlequin mouse holds promise as a model for developing treatments for complex I deficiency syndromes.
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影响因子：
11.4
作者：
Cheung, Eric C. C.;Joza, Nicholas;Slack, Ruth S.
通讯作者：
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影响因子：
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DOI：
10.1073/pnas.96.3.846
发表时间：
1999-02-02
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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